Pharmaceutical product containing arsenic and process of making same



hydroxy-m-amino benzene-arsenic acid "Patented Sept. 20, 1927.

UNITED STATE 8 PATENT. OFF

ICE.

WALTER SCHOELLER AND MAX GEHRKE, OF BERLIN, GERMANY, ASSIGNORS TO FIRE: CHEMISCHE FABRIK AU! ACTIEN (VOBH E. SGHEBING), 01* BERLIN, GERMANY.

PHARMACEUTICAL PRODUCT CONTAINING ARSENIC AND PROCESS OI MAKING SAME.

.No Drawing. Original application filed June 22, 1925, Serial No. 88,902, and in Germany July 2, 1924..

Divided and this application filed Our invention relates to pharmaceutical products and more es ecially to arsinic acld derivatives and to t e. method of making.

in Fargher (Fourn. Chem. -Soc. 115 (1919),

p. 991) obtained 1.2-dihydro benzoxazolon- 4-arsonic acid the arsenic content of which was found to be 28.6 per cent against 28.9 per cent as calculated.

to what could be expected, when working a without any cooling and preferably at a temperature between and 80 degt. there results the symmetrical urea of arsenic content of which was ascertained MOt a Example-If 7.9 grams pydro -mamino-benzene-arsonic acid, dissolvdfl in the form of its sodium salt, are acted u n acid, which can be converted by reduction with ferrous salt into m-(aminobenzoyl amino) p-hydroxy-benzene-arsonic acid. This latter is dissolved in a soda solution and is subjected to the action of'phosgene,

65 until no further diazo reaction can be traced. Upon acidulation there results the symmetrical urea of m-(m-aminobenzoyl bein a yellow amorphous powder soluble in a kalis, but insoluble in the usual or- 75 ganic solvents.

15 We have now ascertained that, contrary NH-CO August 9, 1928. Serial No. 128,334.

to be 30.2 per cent, as against a theoretical ;c0ntent of 30.4 .per cent. This compound corresponds to the formula ASQ1H| MOM,

QNILCO-HNQ H H As comparedwith for instance p-hydroxymacetyl-amino-benzene-arsonie acid, it is more permanently efiective and has a higher chemotherapeutic coeflicient as no saponification-occurs in the organism.

Products which equal, if. not exceed the above in activity, are obtained if p-hydroxym-amino-benzene-arsonic acid is aminoben- 'zoylized and the m-(m-amino-benzoylamino)eg-hydroxy-benzene-arsonic acid is con vert by treating with phosgene into the corresponding urea noun NH-CO-HN amino) p-hydroxy-benzene-arsonic which is a yellow amorphous powder soluble in alkalis, but insoluble in the usual 'organic solvents.

Various changes may be made in the details of the operation and particularly in the proportions of the ingredients present in the solutions used without departing from the invention or sacrificing the advantages thereof.

We claim acid 1. As a new product, the s mmetrical carbonyl urea of m-(m-amino enzoyl amino) p-hydroxy benzene-arsonic acid, correspondmg to the formula tires of a derivative of p-hydrogy-m-ammo- 2. The method of making a symmetrical acidylizing said acid and actin on the prodnot of reaction with phosgene in an alkaline solution while avoiding cooling the reaction mixture.

3. The method of making a symmetrical urea of a derivative of p-hydroxy-m-amino-, benzene-arsonic acid, comprlsmg aminoben zoylizing said acid and acting on the product of reaction with phosgene in an alkaline solution While avoiding cooling the reaction mixture.

4. The method of making a symmetrical urea of a derivative of p-hydroxy-m-aminobenzene-arsenic acid, comprising actmg on said acid with m-nitrobenzoyl chloride, re-

ducing the product I obtained to form m- (amino benzoyl amino) p-hyd'roxy-benzenearsonic acid and acting-on this latter product with phosgene in an alkaline solution while avoiding cooling the reaction mixture.

In testimony whereof we afix our signatures.

WALTER SCHOELLER. MAX GEHRKE. 

